Monday, April 11, 2011

Apoptosis and its role in chemotherapy

The apoptosis is physiological cell death program which could take control the number of normal cells. This is also the way that cancer drugs kill tumor cells.

The apoptosis pathways are controlled by caspases. These inactive substances could be stimulated to active state. There are two main pathways lead to the activation. One is initiated by the ligation of transmembrane death receptors. This could be regulated by c-FLIP through affecting the activator and effector of capases. The other way needs the mitochondrial protein released through the disruption of mitochondria membrane. Capases-9 is activated and thus starts the apoptotic process.

Chemotherapy was used for cancer therapy for more than half a century. But why does it fail sometimes? There are two main reasons: the defects in apoptosis and the drug resistance.

Chemotherapy is expected to only target on the cancer cells by cytotoxic effects. However, sometimes the actual effect is not notable as expected. Also, the normal fast-replicating cells (e.g. bone cells) could be affected.

The tumors cells proliferate much faster than normal cells and this is how they are detected. So, the drugs are used to interfere the DNA replication. Chemotherapeutic agents induce cellular response (e.g. apoptosis) which affects the cell proliferation.

However, thorough the mutation, the gene coding the apoptosis could be changed and thus the tumor cells could get advantages in cell survive and drug resistance. These two factors develop the formation of tumors and affect the effectiveness of chemotherapy.

How does drug action mechanisms work? There are classical drug resistance proteins inside the body which will inhibit the primary drug effect. Depends on its extent, the induced damage would bring in the cells death.But the mutation takes place during this process will develop the multidrug resistance and affect the outcome of chemotherapy.

Jianchao Ge (Student Number: 42572691)


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